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The leukotriene–dendritic cell connection
The Editors’ Choice Donald Y.M. Leung, MD, PhD Harold S. Nelson, MD Stanley J. Szefler, MD William W. Busse, MD
TARC gene is linked to atopy and eosinophilia Thymus and activation-regulated chemokine (TARC) is a crucial TH2-specific chemokine for atopic disorders such as asthma and atopic dermatitis. In this issue of the Journal, Leung et al (p 199) investigate whether a TARC promoter polymorphism is associated with atopy and asthma phenotypes in Chinese children. Peripheral blood eosinophil count and serum total and allergen-specific IgE concentrations were measured, and TARC C-431T genotypes were characterized by restriction fragment length polymorphism. The results showed that this single nucleotide polymorphism was associated with sensitization to Dermatophagoides pteronyssinus and cat as well as with
THE JOURNAL OF
Allergy Clinical Immunology AND
VOLUME 114
NUMBER 1
susceptibility to peripheral eosinophilia among the 387 recruited subjects. Subjects with homozygous TT genotype also had a higher mean serum total IgE concentration and eosinophil percentage. Plasma TARC concentrations were significantly higher in children with asthma than in controls. In the subgroup of asthmatic children, those homozygous for the T allele had significantly higher plasma TARC concentrations in comparison with CT and CC genotypes. The investigators concluded that the C-431T polymorphism in TARC promoter is associated with susceptibility to aeroallergen sensitization and peripheral eosinophilia in Chinese children. This study adds support to the important roles that TARC plays in enhancing TH2mediated allergic inflammation that leads to IgE production and eosinophil recruitment.
The leukotriene–dendritic cell connection In a double-blind, randomized, placebo-controlled clinical trial, Parameswaran et al (p 73) examined a role for cysteinyl leukotrienes in allergen-induced changes in the number of dendritic cells in blood in subjects with asthma. After an allergen inhalation, the number of myeloid dendritic cells (a greater proportion of which express the CysLT1 receptor CysLT1 receptor expression by myeloid and plasmacytoid dendritic cells. than the plasmacytoid cells) rapidly decreased in circulation and the levels of dendritic cell cysteinyl leukotrienes in the migration of myeloid dendritic chemoattractants increased in the airway. This was precells from blood, presumably to the airway. This raises the vented by 2 weeks of treatment with pranlukast, a CysLT1 possibility that long-term treatment with a CysLT1 receptor receptor antagonist. Pranlukast also attenuated the allerantagonist prevents the development of allergy-mediated gen-induced early and late asthma responses and airway airway inflammation. hyperresponsiveness. The results suggest a novel role for
Anaphylactic IgG1, but not nonanaphylactic IgG1, enhances allergic respiratory inflammation Mouse models of allergic respiratory inflammation have shown IgE to potentiate airway responses, but under some experimental conditions this effect could be mediated by IgG1 antibodies. Murine IgG1 antibodies, however, are heterogeneous with regard to their anaphylactic activity and comprise 2 functionally distinct types. In this issue of the Journal, Macedo-Soares et al (p 97) report that reconstitution with the antigen-specific
J ALLERGY CLIN IMMUNOL
anaphylactic type of IgG1, but not reconstitution with the nonanaphylactic type of IgG1, restored lung eosinophilic inflammation and airway hyperreactivity in mice submitted to a B cell–immunosuppressive protocol. These results correlated well with increased levels of cytokines involved in eosinophil migration and activation found in the bronchoalveolar lavage fluid of anaphylactic IgG1–reconstituted mice challenged with antigen. In contrast, nonanaphylactic IgG1–reconstituted mice behaved like those in the nonreconstituted, immunosuppressed group. Thus, anaphylactic properties of IgG1 appear essential for their ability to enhance allergic respiratory inflammation.
July 2004 Page 1
TARC gene is linked to atopy and eosinophilia Thymus and activation-regulated chemokine (TARC) is a crucial TH2-specific chemokine for atopic disorders such as asthma and atopic dermatitis. In this issue of the Journal, Leung et al (p 199) investigate whether a TARC promoter polymorphism is associated with atopy and asthma phenotypes in Chinese children. Peripheral blood eosinophil count and serum total and allergen-specific IgE concentrations were measured, and TARC C-431T genotypes were characterized by restriction fragment length polymorphism. The results showed that this single nucleotide polymorphism was associated with sensitization to Dermatophagoides pteronyssinus and cat as well as with
THE JOURNAL OF
Allergy Clinical Immunology AND
VOLUME 114
NUMBER 1
susceptibility to peripheral eosinophilia among the 387 recruited subjects. Subjects with homozygous TT genotype also had a higher mean serum total IgE concentration and eosinophil percentage. Plasma TARC concentrations were significantly higher in children with asthma than in controls. In the subgroup of asthmatic children, those homozygous for the T allele had significantly higher plasma TARC concentrations in comparison with CT and CC genotypes. The investigators concluded that the C-431T polymorphism in TARC promoter is associated with susceptibility to aeroallergen sensitization and peripheral eosinophilia in Chinese children. This study adds support to the important roles that TARC plays in enhancing TH2mediated allergic inflammation that leads to IgE production and eosinophil recruitment.
The leukotriene–dendritic cell connection In a double-blind, randomized, placebo-controlled clinical trial, Parameswaran et al (p 73) examined a role for cysteinyl leukotrienes in allergen-induced changes in the number of dendritic cells in blood in subjects with asthma. After an allergen inhalation, the number of myeloid dendritic cells (a greater proportion of which express the CysLT1 receptor CysLT1 receptor expression by myeloid and plasmacytoid dendritic cells. than the plasmacytoid cells) rapidly decreased in circulation and the levels of dendritic cell cysteinyl leukotrienes in the migration of myeloid dendritic chemoattractants increased in the airway. This was precells from blood, presumably to the airway. This raises the vented by 2 weeks of treatment with pranlukast, a CysLT1 possibility that long-term treatment with a CysLT1 receptor receptor antagonist. Pranlukast also attenuated the allerantagonist prevents the development of allergy-mediated gen-induced early and late asthma responses and airway airway inflammation. hyperresponsiveness. The results suggest a novel role for
Anaphylactic IgG1, but not nonanaphylactic IgG1, enhances allergic respiratory inflammation Mouse models of allergic respiratory inflammation have shown IgE to potentiate airway responses, but under some experimental conditions this effect could be mediated by IgG1 antibodies. Murine IgG1 antibodies, however, are heterogeneous with regard to their anaphylactic activity and comprise 2 functionally distinct types. In this issue of the Journal, Macedo-Soares et al (p 97) report that reconstitution with the antigen-specific
J ALLERGY CLIN IMMUNOL
anaphylactic type of IgG1, but not reconstitution with the nonanaphylactic type of IgG1, restored lung eosinophilic inflammation and airway hyperreactivity in mice submitted to a B cell–immunosuppressive protocol. These results correlated well with increased levels of cytokines involved in eosinophil migration and activation found in the bronchoalveolar lavage fluid of anaphylactic IgG1–reconstituted mice challenged with antigen. In contrast, nonanaphylactic IgG1–reconstituted mice behaved like those in the nonreconstituted, immunosuppressed group. Thus, anaphylactic properties of IgG1 appear essential for their ability to enhance allergic respiratory inflammation.
July 2004 Page 1